niman wrote:
stephensons wrote:
Quote:
I only get an empty page
The file is large (12MB) and about 25 pages long. It takes a while to load, just be patient. Looks interesting and will take a peak later.
The PB2 E627K Mutation Attenuates Viruses Containing the 2009
H1N1 Influenza Pandemic Polymerase
The paper is an artificial system that says little about pandemic H1N1. The finding that E627K reduces levels of the rescued reassortant, even though E627K is found in the patients in India indicates the experimental results are not applicable to pandemic H1N1.
Here is the key quote from the paper:
We show that in both A549 cell culture and in a mouse model of influenza infection, two of these
changes, PB2-E627K and –D701N, do not potentiate the replication or virulence of a virus
containing the 2009 pandemic RNP. Rather, both of these changes significantly impair the
replication of the virus and diminish the histopathological consequences of infection. Our
findings suggest that if the 2009 pandemic virus were to acquire these changes, greater virulence
would be an unlikely consequence.I think a quick review of this paper and its use by the CDC to proclaim E627K (or D225G) as no problem, is useful. This paper did NOT compare 2009 H1N1 with E627K to 2009 H1N1 without E627K. Instead it used an experimental model that took the four genes in the ribo-nuclear protein complex (PB2, PB2, PA, NP) and put it on a seasonal H1N1 background from 2001. This allowed the RNP with and without E627K to be compared to other RNP's including high and low path H5N1 as well as 1918. In this system the other combinations behaved as expected (taking E627K away from 1918 reduced growth and pathology, while adding E627K to low path H5N1 increased growth and pathology). However, for pandmeic H1N1, the results went the other way - growth was reduced by E627K by 10 to 100 fold.
However, E627K in the patients infected with H1N1 indicate the model did NOT predict the clinical result, becasue a virus that was replication deficient by 10-100 fold would not be able to efficiently tranmit, and would not be found in three patients in the same area over a short time frame. Thus, the expermiental model was NOT predictive of the clinical results, but AFTER the 3 patients with E627K were announced, the CDC used the model to PREDICT that E627K won't be a problem.
Thus, the MODEL is CORRECT and REALITY is NOT!
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okee dokee, but can I mention Kansas and 1918 Swine Flu together? Wasn't Kansas ground zero for the 1918 virus?